Human apolipoprotein A-II is a pro-atherogenic molecule when it is expressed in transgenic mice at a level similar to that in humans: evidence of a potentially relevant species-specific interaction with diet

Abstract

We report on the effect of human apolipoprotein (apo) A-II transgene expression on atherosclerosis susceptibility in two transgenic lines (25.3 and 11.1) whose plasma human apoA-II concentrations (∼23 and 96 mg/dl, respectively) span the normal range in humans. After 9 months of an atherogenic diet, 25.3 and 11.1 transgenic mice developed aortic atherosclerotic lesions that were ∼1.7- and 7-fold, respectively, more extensive than those of non-transgenic control mice. However, there was no difference in the area of atherosclerosis of transgenic and control mice when fed a regular chow diet. This contrasts with the findings in murine apoA-II transgenic mice and provides evidence of a species-specific characteristic that could be of relevance with respect to the high fat intake diets common in most industrialized countries. A possible mechanism of the pro-atherogenic action of human apoA-II could be the inhibition of reverse cholesterol transport and, in support of this, we observed an impairment of apoA-I-HDL particle inter-conversion in the plasma of 11.1 transgenic mice caused, at least in part, by a marked decrease in the endogenous lecithin:cholesterol acyltransferase activity.—Escolà-Gil, J. C., À. Marzal-Casacuberta, J. Julve-Gil, B. Y. Ishida, J. Ordóñez-Llanos, L. Chan, F. Gonzãlez-Sastre, and F. Blanco-Vaca. Human apolipoprotein A-II is a pro-atherogenic molecule when it is expressed in transgenic mice at a level similar to that in humans: evidence of a potentially relevant species-specific interaction with diet.

Keywords

• high density lipoproteins
• atherosclerosis
• apolipoprotein A-I
• lecithin:cholesterol acyltransferase